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Trial record 1 of 318 for:    CLEAR III
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Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00784134
First Posted: November 3, 2008
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.
Emissary International LLC
Information provided by (Responsible Party):
Johns Hopkins University
  Purpose
The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).

Condition Intervention Phase
Intraventricular Hemorrhage Drug: Alteplase Other: Normal saline Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis [ Time Frame: 180 days ]
    Analysis modified on September 29, 2015 to account for adaptive randomization. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Participant Score on the Modified Rankin Scale (mRS) - Ordinal Analysis [ Time Frame: 180 days ]
    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Participants With Modified Rankin Scale (mRS) <=4 - Dichotomized Analysis [ Time Frame: 180 days ]
    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Random Effects Assessment of Site Effect on Modified Rankin Scale (mRS) <= 3 [ Time Frame: 180 days ]
    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3 [ Time Frame: 30 days and 180 days ]
    Comparing longitudinal modified Rankin Scale (mRS) scores 0-3 at Day 30 and Day 180. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).


Secondary Outcome Measures:
  • All Cause Mortality [ Time Frame: 180 days ]
  • Clot Removal (Amount of Residual Blood) [ Time Frame: 72 hours ]
    Change in blood volume measured between stability scan and end of treatment scan

  • Intensity of Critical Care Management - Hospital Days [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - ICU Days [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - ICP Management [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - Mechanical Ventilation [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - Pressors [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - Shunts [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - All Infections [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - Pneumonia [ Time Frame: 30 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Intensity of Critical Care Management - All Infections [ Time Frame: 180 days ]
    Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

  • Safety/Mortality - Mortality Within 30 Days [ Time Frame: 30 days ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  • Safety/Mortality - Bacterial Brain Infections Within 30 Days [ Time Frame: 30 days ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  • Safety/Mortality - Systematic Bleeds Within 72 Hours [ Time Frame: 72 hours ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  • Safety/Mortality - Systematic Bleeds Within 30 Days [ Time Frame: 30 days ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  • Adverse and Serious Adverse Events [ Time Frame: 180 days ]
    Assessment of number of adverse and serious adverse events by treatment group.

  • Predicting Hazards of Death by Treatment Group [ Time Frame: 180 days ]
    Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American) [ Time Frame: 180 days ]
    Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White) [ Time Frame: 180 days ]
    Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic) [ Time Frame: 180 days ]
    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  • Functional Status - Barthel Index [ Time Frame: 180 days ]
    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The Barthel Index (BI) assesses ten functional tasks of daily living, and each task provides a measure for level of independence. Scores range from 0 and 100, with a higher score indicating greater independence.

  • Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability [ Time Frame: 180 days ]
    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The extended Glasgow Outcome Scale (eGOS) is a global scale for functional outcome with eight categories: 1 - Death, 2 - Vegetative State, 3 - Lower Severe Disability, 4 - Upper Severe Disability, 5 - Lower Moderate Disability, 6 - Upper Moderate Disability, 7 - Lower Good Recovery, 8 - Upper Good Recovery.

  • Functional Status - National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: 180 days ]
    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The National Institutes of Health Stroke Scale (NIHSS) is a 15-item scale that assesses language, motor function, sensory loss, consciousness, visual fields, extraocular movements, coordination, neglect, and speech. It is scored from 0 (no stroke symptoms) to 42 (severe stroke).

  • Quality of Life - Stroke Impact Scale (SIS) - Strength [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Mobility [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Hand Function [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Communication [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Thinking [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Emotion [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Participation [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - Stroke Impact Scale (SIS) - Recovery [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  • Quality of Life - EuroQol Visual Analogue Scale (EQ-VAS) [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group. EuroQol Visual Analogue Scale (EQ-VAS) is a self-reported measure of health status. It is a marked scale where individuals draw a line to indicate their health, with end points of 0 (the worst health you can imagine) and 100 (the best health you can imagine).


Enrollment: 500
Study Start Date: July 2009
Study Completion Date: January 2016
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alteplase
administration of alteplase via the intraventricular catheter
Drug: Alteplase
1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Other Names:
  • Cathflo Activase
  • rt-PA
Placebo Comparator: Saline Placebo
1 ml of normal saline administered via the intraventricular catheter
Other: Normal saline
1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-80
  • Symptom onset less than 24 hrs prior to diagnostic CT scan
  • Spontaneous ICH less than or equal to 30 cc or primary IVH
  • IVH obstructing 3rd and/or 4th ventricles
  • ICH clot stability at 6 hours or more post IVC placement
  • IVH clot stability at 6 hours or more post IVC placement
  • Catheter tract bleeding stability 6 hours or more post IVC placement
  • EVD placed per standard medical care
  • SBP less than 200 mmHg sustained for 6 hours prior to drug administration
  • Able to randomize within 72 hours of diagnostic CT scan
  • Historical Rankin of 0 or 1

Exclusion Criteria:

  • Suspected or untreated ruptured cerebral aneurysm, AVM, or tumor
  • Presence of a choroid plexus vascular malformation or Moyamoya
  • Clotting disorders
  • Platelet count less than 100,000, INR greater than 1.4
  • Pregnancy
  • Infratentorial hemorrhage
  • SAH at clinical presentation
  • ICH/IVH enlargement that cannot be stabilized in the treatment time window
  • Ongoing internal bleeding
  • Superficial or surface bleeding
  • Prior enrollment in the study
  • Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
  • Planned or simultaneous participation (between screening and Day-30) in another interventional medical investigation or clinical trial.
  • No subject or legal representative to give written informed consent
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00784134


  Show 81 Study Locations
Sponsors and Collaborators
Johns Hopkins University
National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.
Emissary International LLC
Investigators
Study Chair: Daniel F. Hanley, MD Johns Hopkins University
  More Information

Additional Information:
Study Data/Documents: Data repository-VISTA  This link exits the ClinicalTrials.gov site
Identifier: Data repository-VISTA
when available
Study Protocol  This link exits the ClinicalTrials.gov site
when available
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
when available

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00784134     History of Changes
Other Study ID Numbers: IVH06
5U01NS062851-05 ( U.S. NIH Grant/Contract )
First Submitted: October 31, 2008
First Posted: November 3, 2008
Results First Submitted: March 30, 2017
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Johns Hopkins University:
intraventricular hemorrhage thrombolysis

Additional relevant MeSH terms:
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action